JAK1 mutations were found in 3 B-cell ALL samples after the resequencing of 173 B-ALL (Flex et al., 2008) and in 3 samples after the resequencing of 187 high risk childhood B-ALL (Mullighan et al., 2009). No mutations were found after the resequencing of 69 B-ALL (Jeong et al., 2008).Table 2: Somatic mutations in JAK1 found in B-ALL patients.

Amino acid substitution

Proof of hyperactivity

domain

reference

K204M

FERM

Flex et al., 2008

L624_R629>W

Yes

Pseudokinase

Mullighan et al., 2009

A634D

Yes

Pseudokinase

Flex et al., 2008

S646F

Yes

Pseudokinase

Mullighan et al., 2009

L653F

Pseudokinase

Flex et al., 2008

V658F

Yes

Pseudokinase

Mullighan et al., 2009

R724H

Yes

Pseudokinase

Flex et al., 2008

JAK1 mutants induce the activation of different cytokine-receptor complexes like the IL-9 receptor or the IL-2 receptor, that will induce the constitutive activation of the JAK-STAT pathway.

JAK1 mutations were found in two AML samples after the resequencing of 94 AML (Xiang et al., 2008) and in one AML sample after the resequencing of 105 AML.Table 3: Somatic mutations in JAK1 found in AML samples.